A truncating PET100 variant causing fatal infantile lactic acidosis and isolated cytochrome c oxidase deficiency

Isolated mitochondrial complex IV (cytochrome c oxidase) deficiency is an important cause of mitochondrial disease in children and adults. It is genetically heterogeneous, given that both mtDNA-encoded and nuclear-encoded gene products contribute to structural components and assembly factors. Pathogenic variants within these proteins are associated with clinical variability ranging from isolated organ involvement to multisystem disease presentations. Defects in more than 10 complex IV assembly factors have been described including a recent Lebanese founder mutation in PET100 in patients presenting with Leigh syndrome. We report the clinical and molecular investigation of a patient with a fatal, neonatal-onset isolated complex IV deficiency associated with multiorgan involvement born to consanguineous, first-cousin British Asian parents. Exome sequencing revealed a homozygous truncating variant (c.142C>T, p.(Gln48*)) in the PET100 gene that results in a complete loss of enzyme activity and assembly of the holocomplex. Our report confirms PET100 mutation as an important cause of isolated complex IV deficiency outside of the Lebanese population, extending the phenotypic spectrum associated with abnormalities within this gene.     

Monocytoid B-cell lymphoma: its evolution and relationship to other low- grade B-cell neoplasms

Monocytoid B-cell lymphoma (MBCL) is a newly recognized B-cell neoplasm of uncertain histogenesis. The cytologic features of the neoplastic monocytoid B lymphocytes are virtually identical to those of hairy cell leukemia (HCL). As with HCL, progression of MBCL to a higher histologic grade is very unusual. However, whereas circulating leukemic cells are a characteristic feature of HCL, peripheral blood involvement has not been reported in MBCL. We recently studied a patient with MBCL of the spleen and axillary lymph nodes who developed peripheral blood involvement by MBCL cells. Unlike the cells of HCL, the circulating MBCL cells exhibited strong acid phosphatase activity that was tartrate sensitive. The leukemic cells had the antigenic phenotype IgM lambda, CD20+, CD11c+, CD5-, CD25(TAC)-, and PCA-1-. Immunogenetic studies of both lymph node and peripheral blood cells revealed identical immunoglobulin heavy-chain gene rearrangements. When compared with a series of HCL, the immunophenotype was similar except for the absence of PCA-1 and TAC. Progression of the MBCL to a large cell lymphoma, also expressing IgM lambda, was documented in an abdominal lymph node of this patient. Therefore, although rare, peripheral blood involvement by lymphoma cells may occur during the course of MBCL and should be distinguished from HCL with cytochemical and immunophenotypic studies. In addition, comparison of the clinical, pathologic, and immunologic features of MBCL with those of other low-grade B-cell neoplasms suggests that a close lineage relationship exists between MBCL and HCL.     

Treatment with interleukin-3 plus granulocyte-macrophage colony- stimulating factors improves the selectivity of Ara-C in vitro against acute myeloid leukemia blasts

Hematopoietic growth factors (HGFs) interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) individually have been shown to increase the percentage of acute myeloid leukemia (AML) blasts in S phase and enhance the cytotoxic effects of Ara-C against these blasts in culture. We compared in vitro the effects of a combined treatment with GM-CSF (10 ng/mL) plus IL-3 (10 ng/mL) on the metabolism and cytotoxicity of Ara-C in normal bone marrow mononuclear cells (NBMMC) and AML blasts. NBMMC from six healthy volunteers and AML blasts from 10 patients were incubated for 20 hours with or without IL- 3 plus GM-CSF, followed by a concurrent treatment with Ara-C for 4 additional hours. Exposure to the HGFs and Ara-C produced significantly higher intracellular Ara-CTP levels as well as higher Ara-CTP/dCTP pool ratios in AML blasts as compared with NBMMC. Treatment with HGFs resulted in [3H] Ara-C DNA incorporation that was significantly higher in AML blasts versus NBMMC. This selective improvement of Ara-C metabolism in AML blasts was associated with an enhanced Ara-C-mediated leukemia colony-forming unit (CFU) growth inhibition. In contrast, exposure to HGFs resulted in an improved colony growth of normal CFU granulocyte-monocyte and CFU-granulocyte, erythroid, monocyte, megakaryocyte. These in vitro studies indicate that a combined treatment with IL-3 plus GM-CSF may improve the selectivity of Ara-C against AML blasts.     

Maturational effect on physical capacities and anabolic hormones in under-16 elite footballers: a cross-sectional study

Sport Sciences for Health - The purposes of this study were to describe the fitness and hormonal levels according to playing time (PT) (i.e., PT during season less (PT1) or more (PT2) than 50% of...     

Multiple intrahepatic vascular shunts causing hyperammoniaemic encephalopathy in a patient without liver cirrhosis

The very rare case of a non-cirrhotic patient with multiple intrahepatic portosystemic and arteriosystemic vascular shunts, presenting with hyperammoniaemic type B encephalopathy and hypoalbuminaemia due to proteinuria, is reported. The correct diagnosis, suspected by abdominal ultrasound and colour-Doppler imaging, was confirmed by hepatic and superior mesenteric angiography. A comparison with the few similar cases existing in the literature is offered.     

Neuropsychological and genetic differences between age-associated memory impairment and mild cognitive impairment entities

OBJECTIVE: To neuropsychologically and genetically compare age-associated memory impairment (AAMI) and mild cognitive impairment (MCI) entities and to determine what proportion of AAMI diagnosed individuals could also receive a MCI diagnosis. To compare the distribution of a previously known genetic risk factor for Alzheimer's disease (apolipoprotein E common polymorphism) associated with these two conditions with a sample of the normal aging. DESIGN: Neuropsychological and genetic assessments in AAMI and MCI individuals. Genetic assessment in AAMI, MCI, and control subjects. SETTING: General health centers and geriatric homes from northeastern Spain (Catalunya). PARTICIPANTS: One hundred and four subjects presenting subjective memory complaints were selected and the AAMI and MCI criteria were applied. One hundred and twenty-four healthy Spanish subjects age 50 and older were defined as controls. MEASUREMENTS: Memory, language, and frontal lobe functions were assessed using standard neuropsychological tests. The apolipoprotein E (apo E) polymorphism was obtained by using polymerase chain reaction (PCR) and HhaI restriction endonuclease. RESULTS: Sixty-seven percent of previously diagnosed AAMI individuals could also be identified as MCI subjects. These MCI cases differed from those only-AAMI individuals both in neuropsychological and genetic analyses, performing worse not only on memory but also on language and frontal lobe tests and presenting high and low prevalences of the apo E epsilon 3/epsilon 4 and epsilon 3/epsilon 3 genotypes, respectively. The general AAMI sample of 93 individuals also differed from controls in the apo E genotype and allele distributions but these differences were no longer present after subtracting the MCI cases (63 subjects). These findings reflect that the differences between the memory impaired sample and the control sample regarding the apo E polymorphism were mainly attributable to MCI individuals and not to those who received only a diagnosis of AAMI alone. CONCLUSIONS: Our findings suggest that among AAMI subjects, those who also fulfill the MCI criteria present a neuropsychological and genetic profile closer to that previously related to Alzheimer's disease than those individuals only eligible for a diagnosis of AAMI. However, our findings also suggest that using only the AAMI criteria still appears to select a population that differs genetically from the normal older population.     

SARS-CoV-2 infection after alemtuzumab in a multiple sclerosis patient: milder disease symptoms in comparison with coinfected relatives: a case report and review of the literature

Neurological Sciences - Literature data reporting SARS-CoV-2 infection in multiple sclerosis (MS) patients recently treated with immunodepleting agents as cladribine and alemtuzumab are very...